Efficacy and Safety Evaluation of Amlitelimab Monotherapy in Adults with Severe Alopecia Areata: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study

The primary objective of this study is to evaluate the **efficacy** of amlitelimab compared to placebo in adult participants with severe **alopecia areata** (AA) who have experienced 50% or greater scalp hair loss. The focus is on the regrowth of lost hair, which is clinically relevant as it addresses a significant concern for individuals with AA, potentially improving their psychological well-being and quality of life.

Secondary objectives include:

• Evaluating the efficacy of amlitelimab compared to placebo in improving signs, symptoms, and quality of life in adult participants with AA with 50% or greater scalp hair loss.
• Assessing the **safety** and tolerability of amlitelimab treatment in participants with AA.
• Characterizing the **pharmacokinetic** (PK) profile of amlitelimab administered by subcutaneous injection in participants with AA.
• Characterizing the **immunogenicity** of amlitelimab administered by subcutaneous injection in participants with AA.

The clinical trial involves a total of **129 participants** diagnosed with **alopecia areata**, specifically targeting adult individuals experiencing 50% or greater scalp hair loss. The study population includes both male and female subjects, with an age range that encompasses adults. Participants were selected based on a definitive diagnosis of alopecia areata for more than six months, with severe hair loss affecting at least 50% of the scalp. The trial excludes vulnerable populations and requires participants to maintain a consistent hairstyle and hair care routine, avoiding certain hair products and practices. The selection criteria ensure that participants have stable disease with no significant hair regrowth in the past six months. The trial aims to evaluate the efficacy of amlitelimab compared to placebo in promoting hair regrowth in this specific population.

The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled**, parallel group, 3-arm study to evaluate the efficacy and safety of **amlitelimab** monotherapy administered via **subcutaneous injection** in adult participants with severe **alopecia areata**. The trial is multinational and multicenter, with an estimated recruitment start date of September 1, 2024, and an estimated end date of February 17, 2028. The primary objective is to assess the efficacy of amlitelimab compared to placebo in participants with 50% or greater scalp hair loss, focusing on the regrowth of lost hair. The primary endpoint is the change from baseline in the Severity of Alopecia Tool (SALT) score at Week 36. Secondary endpoints include various measures of hair regrowth and patient-reported outcomes at Weeks 24 and 36.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a definitive diagnosis of alopecia areata for more than six months and severe hair loss affecting at least 50% of the scalp. The trial will include follow-up visits at specified intervals to monitor progress and collect data on efficacy and safety outcomes. The end-of-study visit will conclude the participant's involvement, which is expected to last up to 140 days, corresponding to the maximum treatment period. Conditions that may lead to early termination from the study include significant adverse events or non-compliance with study protocols.

The trial will employ a placebo group to ensure the reliability of the results, with participants randomly assigned to receive either amlitelimab or a matching placebo. The double-blind design ensures that neither the participants nor the investigators know which treatment is being administered, minimizing bias. The study will also monitor the incidence of treatment-emergent adverse events and the presence of anti-drug antibodies at prespecified timepoints. The trial's comprehensive design aims to provide robust data on the potential benefits and risks of amlitelimab for individuals with severe alopecia areata.

The clinical trial involves the administration of **Amlitelimab**, an investigational medication, to evaluate its efficacy and safety in adult participants with severe **alopecia areata**. Amlitelimab is provided as a **solution for injection in a pre-filled syringe**. The active substance, Amlitelimab, is a protein of other origin, developed by Sanofi Aventis Recherche et Développement (SAR). The medication is administered via **subcutaneous injection**. The dosing regimen includes a maximum daily dose of 500 mg, with a total maximum dose of 6750 mg over a treatment period of up to 140 days. The study aims to assess the regrowth of lost hair in participants with 50% or greater scalp hair loss.

In addition to the experimental treatment, the study includes a **placebo** group. The placebo is designed to match the Amlitelimab test product in appearance and administration method, ensuring the study remains double-blind. The placebo is administered in the same pharmaceutical form, a solution for injection in a pre-filled syringe, and via the same route, subcutaneous injection. This allows for a direct comparison of the efficacy and safety of Amlitelimab against the placebo in the study population.

Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment protocol. The trial is structured as a randomized, double-blind, placebo-controlled, parallel-group study, which is standard for evaluating the efficacy of new treatments in a controlled and scientifically rigorous manner.

The efficacy of amlitelimab in the treatment of severe **alopecia areata** will be assessed through a series of primary and secondary endpoints. The primary endpoint is the change from baseline in the Severity of Alopecia Tool (SALT) score at Week 36. Secondary endpoints include changes from baseline in SALT score at Week 24, the proportion of participants achieving a SALT score ≤20 at Weeks 24 and 36, and the time to achieve a SALT score ≤20. Additional secondary endpoints involve the proportion of participants achieving SALT scores ≤10, SALT50, SALT75, and SALT90 at specified timepoints, as well as various patient-reported outcomes (PROs) and clinician-reported outcomes (ClinROs) related to eyebrow and eyelash hair loss.

Measurements will be collected at multiple timepoints, including Weeks 24 and 36, using validated scales such as the SALT score and PRO Scalp Hair Assessment. The study will also evaluate the proportion of participants achieving specific improvements in ClinRO and PRO measures for eyebrow and eyelash hair loss. Furthermore, the study will monitor serum amlitelimab concentrations and the incidence of anti-drug antibodies (ADAs) at prespecified timepoints to assess the pharmacokinetics and immunogenicity of the treatment. The analysis of these endpoints will provide comprehensive data on the efficacy of amlitelimab in promoting hair regrowth in participants with severe alopecia areata.